The low-level laser therapy on muscle injury recovery

Physiotherapy / Fisioterapia
The low-level laser therapy on muscle injury recovery:
literature review
A terapia laser de baixa intensidade na recuperação da lesão muscular: revisão da literatura
Daniel Rodrigues dos Santos1, Richard Eloin Liebano1,2, Cristiano Schiavinato Baldan1,3, Igor Bordello Masson1,
Renato Paranhos Soares3, Ivaldo Esteves Junior1
1
Physiotherapy School, University Paulista, São Paulo-SP, Brazil; 2Physiotherapy School, City University of São Paulo, São Paulo-SP, Brazil;
Physiotherapy School, Methodist University of São Paulo, São Paulo-SP, Brazil.
3
Abstract
The muscle injury recovery process is slow and often changes the original mechanical properties of the damaged muscle. The goal of rehabilitation is to recover the muscle as fast as possible offering the lowest risk of injury recurrence. Among the available therapeutic resources,
the low-level laser therapy (LLLT) has proven to be effective both in reducing the deleterious effects of the acute inflammatory response, as
in the stimulation of the events involved in the repair phase of the muscle recovery process.
Descriptors: Muscles/injuries; Physical therapy; Laser therapy, low-level; Rehabilitation
Resumo
O processo de recuperação de uma lesão muscular é lento e muitas vezes alteram as propriedades mecânicas originais do músculo. O objetivo da reabilitação é recuperar o músculo o quanto antes oferecendo o menor risco possível de recorrência da lesão. Dentre os recursos
terapêuticos disponíveis, a terapia laser de baixa intensidade (TLBI) tem se mostrado extremamente benéfica, tanto na redução dos efeitos
deletérios da resposta inflamatória aguda, quanto na potencialização dos eventos envolvidos na fase de reparação do processo de recuperação da lesão muscular.
Descritores: Músculos/lesões; Fisioterapia; Terapia a laser de baixa intensidade; Reabilitação
Introduction
neration to spread along the fiber and limiting the injury to a local
process8,11.
The main goal of rehabilitation in muscle injuries is to bring the
person back to physical activity as soon as possible offering the lowest risk of injury recurrence1. To achieve this goal, the physiotherapist relies on a wide range of therapeutic resources which can be
used as tools to accelerate the muscle recovery process and promote
the balance between scar tissue formation and muscle regeneration
in a way to provide both strength and torque to the recovered muscle2-4. Among the available resources, the low-level laser therapy
(LLLT) has been proven to be effective both in the modulation of
acute inflammatory response and the secondary damages produced
by it, as in the stimulation of cells involved in the repair phase of the
muscle recovery process5-6.
Inflammatory phase
The first inflammatory signs of a muscle injury may be noted from
the time that some proteases and enzymes such as phospholipase
A2, are activated by extracellular calcium influx. The phospholipase
A2 cleaves the arachidonic acid from phospholipids present in the
sarcolema of the disrupted muscle fibers. In its free form, arachidonic acid may follow two different pathways. One of the leukotrienes, that act on leukocyte chemotaxis and increase of vascular
permeability, and another of cyclooxygenase, which produces prostaglandin E2, a substance that increases vascular permeability and
pain sensitivity in the injured area12-13. The first immune cells to
reach the site of injury are the neutrophils, though their presence
tends to decrease as the population of macrophages increases in the
next couple of days following the injury7-8,12. Besides being responsible for the phagocytosis of necrotic material resulting from the
inflammatory process, neutrophils and macrophages release important chemical factors that operate in the recruitment of satellite
cells which participate actively in the muscle tissue regeneration8,11.
On the other hand, the release of reactive oxygen species due to the
neutrophils respiratory burst may increase the acute inflammatory
response, damaging adjacent healthy cells and expanding the area
of injury8,13. The death of healthy cells during the acute inflammatory phase of muscle injury also occurs by secondary hypoxia due
to the ischemia caused by the rupture of blood vessels, increased
blood viscosity and occlusion of capillaries caused by increased extracellular pressure14.
Literature review
Muscle injuries
Muscle injuries can be caused by different mechanisms and
constitute a major challenge the rehabilitation7. Depending on the
mechanism of injury and its symptoms, muscle injuries can be
classified in contusions, sprains, lacerations8-9 and those induced by
exercise10. However, regardless of the mechanism that caused the
damage, the muscle recovery process always follows the same path
involving specific events that overlap each other: degeneration, inflammation, repair and finally, remodeling8,11.
Degeneration phase
The degeneration phase begins with the rupture of the basal and
plasma membranes of muscle fibers by the mechanism of injury, allowing an influx of extracellular calcium and consequent activation
of intrinsic proteases that cause the autodigestion and necrosis of the
broken fibers12. On the other hand, in the moments following the
injury, a condensation on the cytoskeletal of the broken fibers form
a band of contraction which acts as a buffer, preventing the dege-
J Health Sci Inst. 2010;28(3):286-8
Repair phase
The repair phase of muscle injuries is marked by two simultaneous processes, the regeneration of broken fibers and the formation of scar tissue, so the balance between these two processes is
essential to preserve the original mechanical properties of the inju-
286
red muscle2,4,11. The muscle regeneration occurs through the attraction of satellite cells by chemical factors to the injury site,
where they differentiate into myoblasts to then merge into myotubes and finally mature giving rise to new muscle fibers that fill the
space between the broken fibers9,15. It's not always that the regenerated muscle fibers reconnect to the remaining segments of the
broken fibers, instead they tend to adhere to the extracellular matrix of scar tissue interposed between them9. The formation of scar
tissue starts with the formation of a scaffold of fibrin and fibronectin that acts as anchorage site for the fibroblasts4,11,15. This structure
grows as the fibroblasts firstly synthesize and deposit the fragile fibers of collagen type III and later the fibers of collagen type I, which
is more resistant but less flexible4,11. The formation of extensive fibrosis is a limiting factor in muscle recovery process, since the excess of scar tissue hinders the regeneration of muscle fibers and reduces both the extensibility and contractility of the injured
muscle12,15.
mage some vital cell constituents, such as proteins, lipids and DNA
itself, what hamper the muscle recovery process and harm adjacent
healthy cells, increasing the area of injury7,17,22. However, reactive
oxygen species cannot be seen just as aggressive agents, since they
also act as important secondary messengers in several physiological functions of the cell, such as DNA synthesis and cell proliferation5. The proper application of LLLT is able to reduce excess reactive oxygen species without compromising cell viability, positively
influencing the resolution of the inflammatory process22.
LLLT fibroblast proliferation
Fibroblasts have a wide range of chromophores that can be stimulated by different wavelengths of LLLT23, increasing the release
of basic fibroblast growth factor (FGFb) and insulin-like growth
factor (IGF-1) produced by these cells. These substances are essential for the tissue repair process, since they stimulate both the proliferation and the recruitment of new fibroblasts, enhancing the synthesis of collagen and contributing to the formation of new blood
vessels and important elements of the extracellular matrix24.
Remodeling phase
The last step in the muscle recovery process is the remodeling
phase. At this stage the regenerated muscle fibers contract as the collagen fibers reorganize themselves15 according to the tensions imposed to the muscle. These tensions are extremely important since
they enhance the adhesion of regenerated muscle fibers to the extracellular matrix4 and contribute to reduce the final amount of scar
tissue2,4.
LLLT on muscle regeneration
The satellite cells remain quiescent beneath the basement membrane of muscle fibers and play an important role in muscle regeneration, where they give rise to new fibers that replace those ones
that were damaged by the mechanism of injury25-26. Both in vitro26
as in vivo6,25 studies have confirmed that LLLT favors the regeneration of muscle tissue through the activation of satellite cells by introducing them in the cell cycle that promotes its proliferation and
progression to the status of new muscle fibers6,25-26.
The LLLT
The LLLT refers to the use of monochromatic and coherent light
beams at specific wavelengths able to induce photobiological reactions when absorbed by photoreceptor molecules known as chromophores present in the irradiated body tissues. The photons contained in the laser beam has the ability to change the structure of
chromophores, leading them to electronically excited states that trigger biological processes at cellular level5,16.
Discussion
It is important to take into account that the biological effects observed in the tissues submitted to LLLT depend directly on the
adopted parameters for its application6,20,27-28. The radiant power of
the laser device in Watts, the cross-sectional area of the laser beam
in square centimeters and the irradiation time in seconds, are the basic parameters used to calculate two other parameters that reflect the
dose applied: (1) the energy density in Joules per square centimeter, which is the result of the irradiation power multiplied by the irradiation time and divided by the cross-sectional area of the beam;
(2) the radiant energy in Joules, which is obtained by multiplying the
device radiant power by irradiation time27. The radiant energy is probably the most influent parameter in the treatment outcome since
it represents the total amount of measurable energy inherent to the
photons deposited on each irradiated point27.
Regarding the wavelength, both anti-inflammatory and biostimulatory effects of LLLT may be obtained from different wavelengths between 630 nm and 1064 nm29. The infrared lasers have
greater penetrating power so that a significant portion of its photons
can reach deeper body tissues. In contrast, red-light lasers are more
advantageous in the surface layers, since most of its photons are absorbed by tissues located at this depth25,27.
In the application of a single dose of LLLT (660 nm; 100 mW;
0.03 cm2; 40s; 4J) after a model of exercise induced muscle injury in
rats, biological samples collected between 24 and 48 hours after irradiation showed a significant reduction both in creatine kinase levels, a biomarker for muscle damage, as in the number of cells that
died by apoptosis16. The LLLT (632.8 nm; 0.5 cm2; 600s) with different radiant power of 4 mW; 9 mW and 14 mW, obtaining doses of
2.4J; 5.4J and 8.4J respectively, applied after an injury induced by eccentric muscle contractions in rats, promoted an increase in the antioxidative activity and a significant reduction in the inflammatory response. Nevertheless, the doses of 2.4J and 5.4J significantly reduced
creatine kinase levels only after the second application, whereas
since the first application the dose of 8.4J was able to significantly increase the levels of the antioxidant enzyme superoxide dismutase and
reduce the levels of creatine kinase and malondialdehyde, biomarkers of muscle damage and oxidative stress respectively28.
In surgically induced muscle injury in the gastrocnemius muscle
LLLT on ATP synthesis
In muscle fibers that had its cellular structure compromised by an
injury it has been observed a reduction in the population of mitochondria17, besides the hypothesis that calcium influx caused by
rupture of the sarcolemma also inhibits mitochondrial respiration,
reducing in both situations the availability of intracellular adenosine
triphosphate (ATP)16,18. An analysis of the integrity of intracellular
ATP allows the evaluation of the physiological status of the cell, its
energetic properties, metabolic regulation and also the functionality of its signaling system which is responsible for coordinating several cellular functions19. The photons from LLLT change the molecular conformation of some metal components present in the
enzymatic complexes of the mitochondrial respiratory chain increasing significantly the transfer of electrons along the respiratory
chain and the pumping of protons across the inner membrane of mitochondria, what enhances significantly the ATP production5,20.
The increased availability of ATP provided by LLLT reactivates cellular processes that were inhibited due to the physiological changes triggered by muscle injury, such as the synthesis of DNA, RNA
and proteins which play an important role in the cell proliferation
and muscle recovery processes19-20.
LLLT on the oxidative stress
In a study that compared its anti-inflammatory effects with those
provided by common cyclooxygenase inhibitors drugs, LLLT was
able to reduce reactive oxygen species both directly as through the
antioxidative activity of the superoxide dismutase enzyme, which
decreases the expression of cyclooxygenase reducing the release of
prostaglandins and modulating the inflammatory response21. Although it is known that neutrophils play a key role in the muscle recovery process, the huge increase in reactive oxygen species due to
the neutrophils respiratory burst during acute inflammation may da-
J Health Sci Inst. 2010;28(3):286-8
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The low-level laser therapy on muscle injury
of rats, the application of LLLT (785 nm; 75 mW; 0.07 cm2; 12s; 0.9J)
inhibited the inflammatory response and enhanced fibroblast proliferation, what accelerated the formation of scar tissue and stimulated the activation of satellite cells, thus contributing to the organization of the regenerated muscle fibers6. In an in vitro study, satellite
cells arranged along isolated muscle fibers that received LILT
(632.8 nm; 4.5 mW; 0.18 cm2; 3s; 0.013J) in a single application,
were activated and entered the cell cycle that leads them to the condition of new muscle fibers26. This dose may seem small, but it should
be considered that LLLT was applied directly to the culture dish with
no barrier between the laser beam and the irradiated cells. In rat gastrocnemius muscle, tissue resistance can weaken the radiant power
of a laser beam from 60 mW to 20 mW after it crosses the skin and
cause it to reach with only 5 mW the deeper muscle fibers25.
The beneficial effects of LLLT (904 nm; 700 Hz; 15 mW; 0.2 cm2)
with irradiation times of 7; 20; 67 and 200s, and doses of 0.1; 0.3;
1 and 3J respectively, were also noted in the development of muscle fatigue and blood levels of lactate and creatine kinase when administered previously to a model of electrically induced tetanic contractions in rats. The doses of 1 and 3J were the only ones that
significantly delayed muscle fatigue, and while all doses significantly
reduced the lactate levels, only the dose of 3J did not significantly
reduced the creatine kinase levels. Therefore the dose of 1J was the
only one that showed a significant beneficial effect on all evaluated indexes30. The results achieved in this study are important since
they reveal a preventive potential of LLLT in clinical practice.
10. Serrão FV, Foerster B, Spada S, Morales MM, Monteiro-Pedro V, Tannús A et
al. Functional changes of human quadriceps muscle injured by eccentric exercise. Braz J Med Biol Res. 2003;36(6):781-6.
11. Järvinen TAH, Järvinen TLN, Kääriäinen M, Kalimo H, Järvinen M. Muscle injuries: biology and treatment. Am J Sports Med. 2005;33(5):745-64.
12. Prisk V, Huard J. Muscle injuries and repair: the role of prostaglandins and inflammation. Histol Histopathol. 2003;18(4):1243-56.
13. Connolly DA, Sayers SP, McHugh MP. Treatment and prevention of delayed
onset muscle soreness. J Strength Cond Res. 2003;17(1):197-208.
14. Oliveira NML, Rainero EP, Salvini TF. Three intermittent sessions of cryotherapy reduce the secondary muscle injury in skeletal muscle of rat. J Sports Sci
Med. 2006;5:228-34.
15. Menetrey J, Kasemkijwattana C, Day CS, Bosch P, Vogt M, Fu FH et al. Growth
factors improve muscle healing in vivo. J Bone Joint Surg Br. 2000; 82(1):131-7.
16. Sussai DA, Carvalho PTC, Dourado DM, Belchior ACG, Reis FA, Pereira DM.
Low-level laser therapy attenuates creatine kinase levels and apoptosis during forced swimming in rats. Lasers Med Sci. 2010;25(1):115-20.
17. Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J
Phys Med Rehabil. 2002;81(11 Suppl):S52-69.
18. Cheung K, Hume P, Maxwell L. Delayed onset muscle soreness: treatment
strategies and performance factors. Sports Med. 2003;33(2):145-64.
19. Hu WP, Wang JJ, Yu CL, Lan CC, Chen GS, Yu HS. Helium-neon laser irradiation stimulates cell proliferation through photostimulatory effects in mitochondria. J Invest Dermatol. 2007;127(8):2048-57.
20. Silveira PC, Silva LA, Fraga DB, Freitas TP, Streck EL, Pinho R. Evaluation of mitochondrial respiratory chain activity in muscle healing by low-level laser therapy. J Photochem Photobiol B. 2009;95(2):89-92.
21. Lim W, Lee S, Kim I, Chung M, Kim M, Lim H et al. The anti-inflammatory mechanism of 635 nm light-emitting-diode irradiation compared with existing COX
inhibitors. Lasers Surg Med. 2007;39(7):614-21.
Conclusion
22. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K. Low-level
laser irradiation attenuates production of reactive oxygen species by human neutrophils. J Clin Laser Med Surg. 2003;21(3):165-70.
Noting the correlation between the physiological events involved
in the muscle injury recovery and the scientific evidence of LLLT effects available in the literature, it is possible to verify the therapeutic potential of LLLT at all phases of the muscle recovery process.
While its anti-inflammatory and antioxidative properties have been
shown to be helpful in reducing the deleterious effects of acute inflammation response, its bio-stimulant properties has proven to be
extremely beneficial to the events involved in the repair phase. However, the wide variation observed in the parameters adopted for the
application of LLLT in muscle injuries, makes it clear the need for
future studies to determine which doses are most effective for achieving the best results.
23. Vinck EM, Cagnie BJ, Cornelissen MJ, Declercq HA, Cambier DC. Increased
fibroblast proliferation induced by light emitting diode and low power laser irradiation. Lasers Med Sci. 2003;18(2):95-9.
24. Saygun I, Karacay S, Serdar M, Ural AU, Sencimen M, Kurtis B. Effects of laser
irradiation on the release of basic fibroblast growth factor (bFGF), insulin like
growth factor-1 (IGF-1), and receptor of IGF-1 (IGFBP3) from gingival fibroblasts.
Lasers Med Sci. 2008;23(2):211-5.
25. Nakano J, Kataoka H, Sakamoto J, Origuchi T, Okita M, Yoshimura T. Lowlevel laser irradiation promotes the recovery of atrophied gastrocnemius skeletal
muscle in rats. Exp Physiol. 2009;94(9):1005-15.
26. Shefer G, Partridge TA, Heslop L, Gross JG, Oron U, Halevy O. Low-energy
laser irradiation promotes the survival and cell cycle entry of skeletal muscle satellite cells. J Cell Sci. 2002;115(7):1461-9.
References
27. Enwemeka CS. Intricacies of dose in laser phototherapy for tissue repair and
pain relief. Photomed Laser Surg. 2009;27(3):387-93.
1. Heiderscheit BC, Sherry MA, Silder A, Chumanov ES, Thelen DG. Hamstring
strain injuries: recommendations for diagnosis, rehabilitation, and injury prevention. J Orthop Sports Phys Ther. 2010;40(2):67-81.
28. Liu XG, Zhou YJ, Liu TC, Yuan JQ. Effects of low-level laser irradiation on rat
skeletal muscle injury after eccentric exercise. Photomed Laser Surg.
2009;27(6):863-9.
2. Faria FE, Ferrari RJ, Distefano G, Ducatti AC, Soares KF, Montebelo MI et al. The
onset and duration of mobilization affect the regeneration in the rat muscle. Histol Histopathol. 2008;23(5):565-71.
29. Bjordal JM, Lopes-Martins RA, Joensen J, Couppe C, Ljunggren AE, Stergioulas A et al. A systematic review with procedural assessments and meta-analysis of
low level laser therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord. 2008;9:75.
3. Orchard J, Best TM. The management of muscle strain injuries: an early return
versus the risk of recurrence. Clin J Sport Med. 2002;12(1):3-5.
4. Kääriäinen M, Järvinen T, Järvinen M, Rantanen J, Kalimo H. Relation between
myofibers and connective tissue during muscle injury repair. Scand J Med Sci
Sports. 2000;10(6):332-7.
30. Leal Junior EC, Lopes-Martins RA, Almeida P, Ramos L, Iversen VV, Bjordal JM.
Effect of low-level laser therapy (GaAs 904 nm) in skeletal muscle fatigue and biochemical markers of muscle damage in rats. Eur J Appl Physiol. 2010;
108(6):1083-8.
5. Gao X, Xing D. Molecular mechanisms of cell proliferation induced by low
power laser irradiation. J Biomed Sci. 2009;16(1):4.
6. Cressoni MD, Dib Giusti HH, Casarotto RA, Anaruma CA. The effects of a 785nm AlGaInP laser on the regeneration of rat anterior tibialis muscle after surgically-induced injury. Photomed Laser Surg. 2008;26(5):461-6.
Corresponding author:
Ivaldo Esteves Junior
Physiotherapy School
University Paulista – São Paulo
Rua Dr. Bacelar, 1212 - Vila Clementino
São Paulo-SP, CEP 04026-002
Brazil
7. Toumi H, Best TM. The inflammatory response: friend or enemy for muscle injury? Br J Sports Med. 2003;37(4):284-6.
8. Smith C, Kruger MJ, Smith RM, Myburgh KH. The inflammatory response to
skeletal muscle injury: illuminating complexities. Sports Med. 2008;38(11):94769.
E-mail: [email protected]
9. Järvinen TA, Järvinen TL, Kääriäinen M, Aärimaa V, Vaittinen S, Kalimo H et al.
Muscle injuries: optimising recovery. Best Pract Res Clin Rheumatol. 2007;
21(2):317-31.
Santos DR, Liebano RE, Baldan CS, Masson IB, Soares RP, Esteves Junior I.
Received May 17, 2010
Accepted July 5, 2010
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